Targeting the AURKB-MAD2L2 Axis Disrupts the DNA Damage Response and Glycolysis to Inhibit Colorectal Cancer...

Area of Science:

• Molecular Oncology
• Cancer Metabolism
• DNA Damage Response

Background:

• Colorectal cancer (CRC) progression is associated with dysregulated glycolysis and impaired DNA damage response (DDR).
• The genes MAD2L2 and AURKB are implicated in cell cycle regulation and DDR, representing potential therapeutic targets in CRC.

Purpose of the Study:

• To investigate the role of AURKB in colorectal cancer (CRC) progression.
• To explore the relationship between AURKB, MAD2L2, glycolysis, and DDR in CRC.
• To evaluate the therapeutic potential of targeting the AURKB-MAD2L2 axis in CRC.

Main Methods:

• Differential gene expression analysis using TCGA-COAD and GSE47074 datasets.
• Establishment of a predictive risk model for CRC prognosis.
• In vitro knockdown experiments of AURKB in CRC cell lines, assessing cell behavior, oxidative stress, glycolysis, DDR, and interaction with MAD2L2.

Main Results:

• A six-gene prognostic model including AURKB was identified and significantly expressed in CRC tumors.
• AURKB knockdown inhibited CRC cell proliferation, induced G1 cell cycle arrest, increased oxidative stress and apoptosis, and impaired glycolysis.
• MAD2L2 overexpression partially reversed the effects of AURKB knockdown, restoring glycolytic activity and mitigating cell cycle arrest and DDR.

Conclusions:

• AURKB plays a critical role in regulating CRC progression by modulating glycolysis and DDR pathways.
• The AURKB-MAD2L2 axis represents a promising therapeutic target for CRC, potentially disrupting essential metabolic and DNA repair mechanisms.